While anti-DNA antibodies are clearly implicated in pathogenesis in the disease systemic lupus erythematosus, some fundamental question about these antibodies remain unanswered. We are just beginning to understand the structural basis for DNA binding. The question will be pursued in two well defined idiotype systems, one murine and one human, using the technique of site directed mutagenesis. Secondly, we will study the structural basis for renal pathogenicity of anti-DNA antibodies. Finally we hope to adapt techniques of bacterial genetics to the generation of somatically mutated antibody genes and to characterize the protein products for idiotypy and antigen binding.